DRAFT - DO NOT CITE OR QUOTE	lNCEA tradan" dr"f's
or EPA ID for final]
www.epa.gov/iris
4>EPA
ANNOTATED REFERENCE OUTLINE
FOR THE TOXICOLOGICAL REVIEW
OF
2,3,4-T rimethylpentane
(CAS No. 565-75-3)
In Support of Summary Information on the
Integrated Risk Information System (IRIS)
12/22/08
[author: insert current date for this draft or Agency completion date (month and year) iffinal]
NOTICE
This document is a [author: insert Agency Review or external review] draft. It has not been
formally released by the U.S. Environmental Protection Agency and should not at this stage be
construed to represent Agency position on this chemical. It is being circulated for review of its
technical accuracy and science policy implications.
U.S. Environmental Protection Agency
Washington, DC

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REVIEWS
Abraham, MH; Ibrahim, A. (2006) Air to fat and blood to fat distribution of volatile organic
compounds and drugs: Linear free energy analyses. European Journal of Medicinal Chemistry
41(12): 1430-1438.
Abraham, MH; Ibrahim, A; Acree, WE, Jr. (2005) Air to blood distribution of volatile organic
compounds: A linear free energy analysis. Chem Res Toxicol 18:904-911.
ACGIH. (2001) Octane, all isomers. ACGIH. Documentation of the threshold limit values and
biological exposure indices Cincinnati, OH: American Conference of Governmental Industrial
Hygienists; p. 2.
ACGIH. (2007) Octane, all isomers. Threshold limit values for chemical substances and physical
agents and biological exposure indices. Cincinnati, OH: American Conference of Governmental
Industrial Hygienists; p. 45.
Carreon, T (2001) Aliphatic hydrocarbons. In: Bingham, E; Cohrssen, B; Powell, CH; et al.;
eds. Patty's toxicology. John Wiley & Sons, Inc.
2. CHEMICAL AND PHYSICAL INFORMATION
Wilson, EW, Jr.; Hamilton, WA; Kennington, HR; et al. (2006) Measurement and estimation of
rate constants for the reactions of hydroxyl radical with several alkanes and cycloalkanes. J Phys
Chem A 110(10):3593-3604.
3. TOXICOKINETICS
3.1.	ABSORPTION
American Petroleum Institute. (1987) Studies on the absorption of inhaled hydrocarbon vapors
(final report). Submitted under TSCA section FYI; NTIS no. OTS0000488.
Dahl, AR; Damon, EG; Mauderly, JL; et al. (1988) Uptake of 19 hydrocarbon vapors inhaled by
f344 rats. Fundam Appl Toxicol 10(2):262-269.
3.2.	DISTRIBUTION
Abraham, MH; Ibrahim, A. (2006) Air to fat and blood to fat distribution of volatile organic
compounds and drugs: Linear free energy analyses. European Journal of Medicinal Chemistry
41(12): 1430-1438.
Abraham, MH; Ibrahim, A; Acree, WE, Jr. (2005) Air to blood distribution of volatile organic
compounds: A linear free energy analysis. Chem Res Toxicol 18:904-911.
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Meulenberg, CJ; Vijverberg, HP. (2000) Empirical relations predicting human and rat tissue: Air
partition coefficients of volatile organic compounds. Toxicol Appl Pharmacol 165(3):206-216.
3.3. METABOLISM
Delraso, NJ; Mattie, DR; Godin, CS. (1989) In vitro toxicity of solubilized 2,3,4-
trimethylpentane. I. Cytotoxicity and metabolism of tmp using primary hepatocytes. In Vitro
Cell Dev Biol 25(11): 1031-1038.
DelRaso, NJ; Mattie, DR; Godin, CS. (1990) Lack of detectable metabolism for solubilized
2,3,4-trimethylpentane by rat kidney proximal tubules. Toxicol Lett 54(2-3):337-344.
Olson, CT; Hobson, DW; Yu, KO; et al. (1987) The metabolism of 2,3,4-trimethylpentane in
male fischer-344 rats. Toxicol Lett 37(3): 199-202.
Yu, KO; Olson, CT; Hobson, DW; et al. (1987) Identification of urinary metabolites in rats
exposed to the nephrotoxic agent 2,3,4-trimethylpentane. Biomed Environ Mass Spectrom
14(11):639-641.
3.4. ELIMINATION
Olson, CT; Hobson, DW; Yu, KO; et al. (1987) The metabolism of 2,3,4-trimethylpentane in
male fischer-344 rats. Toxicol Lett 37(3): 199-202.
Phillips, M; Greenberg, J; Awad, J. (1994) Metabolic and environmental origins of volatile
organic compounds in breath. Journal of Clinical Pathology (London) 47(11): 1052-1053.
Phillips, M; Herrera, J; Krishnan, S; et al. (1999) Variation in volatile organic compounds in the
breath of normal humans. Journal of Chromatography B 729(l-2):75-88.
Yu, KO; Olson, CT; Hobson, DW; et al. (1987) Identification of urinary metabolites in rats
exposed to the nephrotoxic agent 2,3,4-trimethylpentane. Biomed Environ Mass Spectrom
14(11):639-641.
3.5. PHYSIOLOGICALLY BASED TOXICOKINETIC MODELS
4. HAZARD IDENTIFICATION
4.1. STUDIES IN HUMANS—EPIDEMIOLOGY, CASE REPORTS, CLINICAL
CONTROLS
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4.2. LESS-THAN-LIFETIME AND CHRONIC STUDIES AND CANCER BIOASSAYS
IN ANIMALS—ORAL AND INHALATION
4.2.1. Oral
Bruner, RH; Pitts, LL (1983) Nephrotoxicity of hydrocarbon propellants to male, Fischer-344
rats. Available online at http://handle.dtic.mi1/100.2/ADP001983. Accessed on December 17,
2008.
Norton, WN; Mattie, DR. (1987) The cytotoxic effects of trimethylpentane on rat renal tissue.
Scanning Microsc l(2):783-790.
4.2.2. Inhalation
4.3. REPRODUCTIVE/DEVELOPMENTAL STUDIES—ORAL AND INHALATION
4.4. OTHER ENDPOINT-SPECIFIC STUDIES
Delraso, NJ; Mattie, DR; Godin, CS. (1989) In vitro toxicity of solubilized 2,3,4-
trimethylpentane. I. Cytotoxicity and metabolism of tmp using primary hepatocytes. In Vitro
Cell Dev Biol 25(11): 1031-1038.
DelRaso, NJ; Mattie, DR; Godin, CS. (1990) Lack of detectable metabolism for solubilized
2,3,4-trimethylpentane by rat kidney proximal tubules. Toxicol Lett 54(2-3):337-344.
Mattie, DR; Maslanka, JJ; DelRaso, NJ; et al. (1989) Effect of 2,3,4-trimethylpentane on the
ultrastructure of proximal tubular cells in primary cell culture. U.S. Department of Commerce.
Washington, DC. NTIS/ADA359960.
4.4.1. ACUTE AND SHORT-TERM TOXICITY
4.4.2. GENOTOXICITY STUDIES
4.4.3. NEUROTOXICITY STUDIES
4.4.4. ENDOCRINE DISRUPTION
4.4.5. CONTACT SENSITIZATION
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4.5.	MECHANISTIC DATA AND OTHER STUDIES IN SUPPORT OF THE MODE OF
ACTION
Aschmann, SM; Arey, J; Atkinson, R. (2004) Products and mechanism of the reaction of OH
radicals with 2,3,4-trimethylpentane in the presence of no. Environ Sci Technol 38(19):5038-
5045.
4.6.	SYNTHESIS OF MAJOR NONCANCER EFFECTS
4.6.1.	Oral
4.6.2.	Inhalation
4.6.3.	Mode of Action Information
4.7.	EVALUATION OF CARCINOGENICITY
4.7.1.	Summary of Overall Weight-of-Evidence
4.7.2.	Synthesis of Human, Animal, and Other Supporting Evidence
4.7.3.	Mode of Action Information
4.7.2.1.	Hypothesized Mode of Action
4.7.2.2.	Experimental Support for the Hypothesized Mode of Action
4.7.2.3.	Other Possible Modes of Action
4.7.2.4.	Conclusions About the Hypothesized Mode of Action
4.8.	SUSCEPTIBLE POPULATIONS AND LIFE STAGES
4.8.3. Other
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